title: Interleukin-6 induces Gr-1+CD11b+ myeloid cells to suppress CD8+ T cell-mediated liver injury in mice.
abstract: BACKGROUND
  Agonist antibodies against CD137 (4-1BB) on T lymphocytes are used to increase host anti-tumor immunity, but often leading to severe liver injury in treated mice or in patients during clinical trials. Interleukin-6 (IL-6) has been reported to protect hepatocyte death, but the role of IL-6 in protecting chronic T cell-induced liver diseases is not clearly defined due to lack of relevant animal models. We aimed to define the role of IL-6 in CD8+ T cell-mediated liver injury induced by a CD137 agonistic mAb (clone 2A) in mice.
  
  
  RESULTS
  We expressed IL-6 in the liver by hydrodynamic gene delivery in mice treated with 2A or control mAb and studied how IL-6 treatment affected host immunity and T cell-mediated liver injury. We found that ectopic IL-6 expression in the liver elevated intrahepatic leukocyte infiltration but prevented CD8+ T cell-mediated liver injury. In IL-6 treated mice, CD8+ T cells proliferation and IFN-γ expression were inhibited in the liver. We discovered that IL-6 increased accumulation of Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) in the liver and spleen. These MDSCs had the ability to inhibit T cells proliferation and activation. Finally, we showed that the MDSCs were sufficient and essential for IL-6-mediated protection of anti-CD137 mAb-induced liver injury.
  
  
  CONCLUSIONS
  We concluded that IL-6 induced Gr-1+CD11b+ MDSCs in the liver to inhibit T cell-mediated liver injury. The findings have defined a novel mechanism of IL-6 in protecting liver from CD8+ T cell-mediated injury.
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaozhu
authors.initials: X
authors.lastname: Li
authors.forename: Qiao
authors.initials: Q
authors.lastname: Xing
authors.forename: Peishuang
authors.initials: P
authors.lastname: Du
authors.forename: Lishan
authors.initials: L
authors.lastname: Su
authors.forename: Shengdian
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008107:Liver Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology; D019707:Receptors, Chemokine / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013163:Splenomegaly
chemical_list: D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D015850:Interleukin-6; D020011:Protective Agents; D019707:Receptors, Chemokine